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Background  Over the last decade, the incidence of confirmed malaria has declined significantly in Nepal. The aim of this paper is to assess the spatio-temporal distribution of malaria and its association with climatic factors and vector control interventions in two high-risk districts of Nepal.    Methods  Hotspot analysis was used to visualize the spatio-temporal variation of malaria incidence over the years at village level and generalized additive mixed models were fitted to assess the association of malaria incidence with climatic variables and vector control interventions.    Results  Opposing trends of malaria incidence were observed in two high-risk malaria districts of eastern and far-western Nepal after the introduction of long-lasting insecticidal nets (LLINs). The confirmed malaria incidence was reduced from 2.24 per 10,000 in 2007 to 0.31 per 10,000 population in 2011 in Morang district but increased from 3.38 to 8.29 per 10,000 population in Kailali district. Malaria hotspots persisted mostly in the same villages of Kailali district, whereas in Morang district malaria hotspots shifted to new villages after the introduction of LLINs. A 1° C increase in minimum and mean temperatures increased malaria incidence by 27% (RR =1.27, 95% CI =1.12-1.45) and 25% (RR =1.25, 95% CI =1.11-1.43), respectively. The reduction in malaria incidence was 25% per one unit increase of LLINs (RR =0.75, 95% CI =0.62-0.92). The incidence of malaria was 82% lower in Morang than in Kailali district (RR =0.18, 95% CI =0.11-0.33).    Conclusions  The study findings suggest that LLIN coverage should be scaled up to entire districts rather than high-incidence foci only. Climatic factors should be considered for malaria micro-stratification, mosquito repellents should be prescribed for those living in forests, forest fringe and foothills and have regular visits to forests, and imported cases should be controlled by establishing fever check posts at border crossings.    Electronic supplementary material  The online version of this article (doi:10.1186/1475-2875-13-457) contains supplementary material, which is available to authorized users.

Spatio-temporal distribution of malaria and its association with climatic factors and vector-control interventions in two high-risk districts of Nepal